Abstract: | Golgi antiapoptotic protein (GAAP) is a novel regulator of cell death that is highly conserved in eukaryotes and present in some poxviruses, but its molecular mechanism is unknown. Given that alterations in intracellular Ca2+ homeostasis play an important role in determining cell sensitivity to apoptosis, we investigated if GAAP affected Ca2+ signaling. Overexpression of human (h)-GAAP suppressed staurosporine-induced, capacitative Ca2+ influx from the extracellular space. In addition, it reduced histamine-induced Ca2+ release from intracellular stores through inositol trisphosphate receptors. h-GAAP not only decreased the magnitude of the histamine-induced Ca2+ fluxes from stores to cytosol and mitochondrial matrices, but it also reduced the induction and frequency of oscillatory changes in cytosolic Ca2+. Overexpression of h-GAAP lowered the Ca2+ content of the intracellular stores and decreased the efficacy of IP3, providing possible explanations for the observed results. Opposite effects were obtained when h-GAAP was knocked down by siRNA. Thus, our data demonstrate that h-GAAP modulates intracellular Ca2+ fluxes induced by both physiological and apoptotic stimuli. |